title: Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model.
abstract: OBJECTIVE
  Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear.
  
  
  OBJECTIVE
  We investigated the direct effects of caffeine on hepatic stellate cells (HSCs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis.
  
  
  METHODS
  Human hepatic stellate cell line, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and levels of procollagen type Ic and α-smooth muscle actin (α-SMA) were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation.
  
  
  RESULTS
  Caffeine increased HSCs apoptosis and intracellular F-actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type Ic and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P < 0.05), and fibrosis (2.1 ± 0.35 vs 2.9 ± 0.84, P < 0.05). Transforming growth factor-β and α-SMA expressions were also reduced by caffeine.
  
  
  CONCLUSIONS
  Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation.
authors.affiliation: Department of Gastroenterology, Hanyang University Medical Center, Seoul, Korea.
authors.forename: Sung Gon
authors.initials: SG
authors.lastname: Shim
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Jun
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Waqar Khalid
authors.initials: WK
authors.lastname: Saeed
authors.forename: Kang Nyeong
authors.initials: KN
authors.lastname: Lee
authors.forename: Hang Lak
authors.initials: HL
authors.lastname: Lee
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Lee
authors.forename: Ho Soon
authors.initials: HS
authors.lastname: Choi
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoon
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism; D011347:Procollagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D010446:Peptide Fragments; D011347:Procollagen; D016212:Transforming Growth Factor beta; C042813:procollagen type I carboxy terminal peptide; D002110:Caffeine; D000242:Cyclic AMP
keywords: TGF-β; adhesion; caffeine; liver fibrosis; stellate cell